Date of Award

1-1-2011

Document Type

Masters Thesis

Degree Name

M.S.

Organizational Unit

College of Natual Science and Mathematics

First Advisor

Nancy M. Lorenzon, Ph.D.

Second Advisor

Joseph Angleson

Third Advisor

John Kinnamon

Fourth Advisor

Dwight Smith

Keywords

Calcium, Cerebellum, Malignant hyperthermia, Purkinje neurons, Ryanodine receptor

Abstract

To investigate the etiology of malignant hyperthermia and central core disease, mouse models have recently been generated and characterized (Chelu et al., 2006). These RyRY522S/+ knock-in mutant mice provide an excellent tool to investigate calcium dysregulation, its pathological consequences, and potential therapeutic approaches. Skeletal muscle harboring this mutation exhibits calcium leak from internal stores and an increased sensitivity to activation by caffeine, voltage, and temperature (Durham et al., 2008). Although alterations in RyR1 channel function and resultant changes in cellular function have been characterized in skeletal muscle, the effects of MH mutations in RyR1 on central nervous system function have not been investigated. Since RyR1 is highly expressed in cerebellar Purkinje neurons, our goal is to investigate whether the RyRY522S/+ mutation causes altered calcium handling and whether potential calcium dysregulation alters cellular function.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

George C. Talbott

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

61 p.

Discipline

Biology, Neurosciences



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